Determination of Drug Toxicity Using 3D Spheroids Constructed From an Immortal Human Hepatocyte Cell Line

Numerous publications have documented that the immortal cells grown in three-dimensional (3D) cultures possess physiological behavior, which is more reminiscent of their parental organ than when the same cells are cultivated using classical two-dimensional (2D) culture techniques. The goal of this study was to investigate whether this observation could be extended to the determination of LD50 values and whether 3D data could be correlated to in vivo observations. We developed a noninvasive means to estimate the amount of protein present in a 3D spheroid from it is planar area (± 21%) so that a precise dose can be provided in a manner similar to in vivo studies. This avoided correction of the actual dose given based on a protein determination after treatment (when some cells may have lysed). Conversion of published in vitro LC50 data (mM) for six common drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic acid) to LD50 data (mg compound/mg cellular protein) showed that the variation in LD50 values was generally less than that suggested by the original LC50 data. Toxicological analysis of these six compounds in 3D spheroid culture (either published or presented here) demonstrated similar LD50 values. Although in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D spheroid data resulted in a much higher degree of correlation with in vivo lethal blood plasma levels. These results corroborate that 3D hepatocyte cultures are significantly different from 2D cultures and are more representative of the liver in vivo

Comparative mechanisms of zearalenone and ochratoxin A toxicities on cultured HepG2 cells: Is oxidative stress a common process?

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Toxicities induced in cultured human hepatocarcinoma cells exposed to ochratoxin A: oxidative stress and apoptosis status

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Development, characterization, and biological assessment of biocompatible cellulosic wound dressing grafted Aloe vera bioactive polysaccharide

International audienceIn order to improve healthcare of injured people, deacetylated acemannan extracted from Aloe vera leaves, having high inhibitory properties, was used as an antimicrobial finish on traditional cotton items. Response surface methodology was employed to define quadratic relationships between the polysaccharide grafting degree and the treatment process properties. An optimized modification process, offering the highest funtionalization degree, is obtained. The cellulosic fiber morphology and roughness modifications induced by polymer grafting are revealed using Atomic Force Microscopy and Scanning Electron Microscopy. Infra Red spectroscopy was used to confirm the grafting effectiveness. Thermogravimetric Analysis and Differential Scanning Calorimeter were further employed to confirm chemical modification. Considering the potential use of this new biomaterial, original properties were also studied. Finishing treatment seems to preserve mechanical properties, and hydrophilicity of the cellulosic substrate. MTT assay were done in HepG2 cells to ensure that the obtained dressings are non-toxic. The biomaterial showed high biocompatibility and promoted cell viability. Antimicrobial studies showed that grafting treatment conserved polymer antibacterial activity. Optimized cotton dressings exhibited a significant inhibitory effect against Staphylococcus aureus and Escherichia coli bacteria, killed respectively at 70.2% and 72.4%